The average American is exposed daily to concentrations of fluoride ranging from 0.1 - 12,300 ppm of which some is ingested. The ingested fluoride can elevate the plasma fluoride to peak values from 10 - 100 MuM. Experiments from this laboratory and others have shown that fluoride can enter cells and alter enzymatic activity. It is proposed to continue to examine the effects of fluoride on isolated cells, isolated tissues and intact animals to obtain more information on the possible metabolic effects of fluoride. Towards the aims of learning more about the metabolic and physiologic effects of fluoride the following parameters will be examined (a) to examine the conditions such as transmembrane pH and polarity of an organic phase on fluoride diffusion through a simulated membrane, (b) to determine the effect of NaF on cAMP formation, protein phosphorylation, and glucose metabolism in smooth muscle, (c) to examine the effect of acidosis and alkalosis on fluoride retention and metabolism, (d) to continue examining the effect of fluoride on isolated liver cell metabolism, and (e) to examine the effect of NaF on salivary gland metabolism (amylase release, cAMP production, and glucose metabolism).